Moderate Intellectual Disability Research Articles

Exploring 17q12 Deletion Syndrome: A Case Report of Neurodevelopmental, Endocrine, and Genital Anomalies

Objective − 17q12 deletion syndrome is a rare genetic disease characterized by neurodevelopmental disorders, genital and renal abnormalities, and maturity-onset diabetes of the young type 5 (MODY5).Case Report − This case report details the case of a 13-year-old female with moderate intellectual disability, Mayer-Rokitansky-Küster-Hauser syndrome, multicystic dysplastic kidneys, and MODY5. Genetic testing revealed a 1.52-megabase heterozygous deletion on chromosome 17q12, encompassing the HNF1B and LHX1 genes, which was found to be inherited from the mother. Conclusion − This case underscores the importance of early genetic testing and multidisciplinary approach in managing the multisystemic manifestations of 17q12 deletion syndrome. Early diagnosis and appropriate management are crucial for improving the outcomes and quality of life for affected individuals.

Pineal gland volume in children with intellectual disability.

Pineal gland volume (PGV), which is associated with sleep and circadian rhythm, is known to be changed in some psychiatric disorders such as major depression, mood disorders and schizophrenia. This study aimed to compare the PGV of children with mild and moderate intellectual disability (ID) and healthy children. This multicentre retrospective study included 40 children with ID (patient group), aged 6-12 years and 40 age- and sex-matched healthy children (control group). The children were examined for their sociodemographic characteristics and for PGV using magnetic resonance imaging. The PGV of the patient group was significantly larger than that of the controls (p = 0.023). There was no statistically significant difference in PGV between mild and moderate ID. A moderate and positive correlation was found between Weschler Intelligence Scale for Children-revised (WISC-R) performance score and PGV (p = 0.049, r = 0.313) only in the patient group. In the receiver operating characteristic analysis, the area under the curve was 0.648, and the sensitivity was 70.0%, and the specificity was 60.0%. In conclusion, this study demonstrated that the increased PGV levels were associated with autism spectrum disorder (ASD) and PGV could be a risk factor in the aetiology of ID. Further research with larger sample sizes is needed to clarify this issue.

Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report

The incidence of hypomyelinating leukodystrophies is approximately 1 in every 250,000–500,000 individuals in the population. Hypomyelinating leukodystrophy-8 (HLD-8) is characterized by classical clinical features, including modest intellectual deficits and early-onset progressive cerebellar ataxia, with or without oligodontia and/or hypogonadotropic hypogonadism. In this case report, we present a 34-year-old male who experienced gradually progressive behavioral and memory disturbances over the past 10 years, accompanied by imbalance while walking and complex partial seizures. The patient also exhibited oligodontia and moderate intellectual disability (IQ score: 45). Spasticity was observed in the lower limbs, with exaggerated deep tendon reflexes in all four limbs, and bilaterally extensor plantar responses were noted. Sensory examination results were within normal limits. Bilateral cerebellar signs were present, including gaze-evoked nystagmus in all directions, which was non-fatigable. MRI brain revealed generalized cerebral and cerebellar atrophy, as well as diffuse hyperintensities in T2-weighted images (T2W) and fluid-attenuated inversion recovery (FLAIR) in the bilateral cerebral white matter, with no basal ganglia involvement. The sagittal T1-weighted image (T1W) showed diffuse thinning of the corpus callosum. Whole-exome sequencing revealed a novel variant mutation of the POLR3B gene in HLD-8, specifically in Exon 20 [c.2125A>G (p.Met709Val)] and Exon 23 [c.2699G>A (p.Arg900His)]. Very few case reports and variant mutations on the POLR3B gene on chromosome 12q23.3 have been reported thus far.

Effectiveness of a Three-Step Decoding Strategy with Constant Time-Delay to Teach Word Reading to Students with Mild and Moderate Intellectual Disability

The purpose of this study was to examine the effects of a three-step decoding strategy with constant time delay on teaching and acquisition of decoding and word reading skills to four students with mild and moderate intellectual disability and to measure the generalization of those skills to untaught words. A multiple probe design across participants was used to examine the percentage of sounds correctly decoded and words correctly read. The results indicate that all four participants learned to decode and read words using the two strategies. Furthermore, all participants showed an increased learning efficiency in decoding and reading when teaching the second set of similar words. Generalization data showed that only two participants were able to decode and read some of the new words before teaching them, while all participants' ability to decode the letters of the new words was improved. Keywords: Reading, Phonics, Three-step decoding, Time delay, Intellectual disability

Feasibility, Experiences and Short-Term Outcomes on Challenging Behaviour and Well-Being of a Partially Online Music Intervention Pilot Study for Adults With Intellectual Disabilities.

During the COVID-19 pandemic we implemented a partially online music intervention to examine the feasibility, experiences and short-term outcomes on the challenging behaviour and well-being of adults with intellectual disabilities. This mixed-methods study included 10 participants with mild or moderate intellectual disabilities who received 16 one-hour individual music sessions in 10 weeks, either face-to-face or online. Data on feasibility and experiences from participants and music workers were collected and analysed using inductive thematic analysis. Challenging behaviour and well-being were measured before and after intervention. Overall experiences were positive and concerned appreciation, positive feelings, musical abilities, attention span, relatedness and personalisation. Online experiences varied, but most participants preferred face-to-face over online sessions. After the intervention, challenging behaviour scores were better than before. Engaging in a partially online music intervention is feasible for people with intellectual disabilities and seems to improve challenging behaviour. Experiences are discussed and recommendations for future online sessions are provided.

Changes in the prevalence of intellectual disability among 10-year-old children in Sweden during 2011 through 2021: a total population study

BackgroundRecent studies have suggested an increasing prevalence of intellectual disability diagnoses in some countries. Our aim was to describe the trend in the prevalence of intellectual disability diagnoses in Sweden and explore whether associated sociodemographic and perinatal factors can explain changes in the prevalence.MethodsWe used a register-based nationwide cohort of residents in Sweden born between 2001 and 2011. We calculated the prevalence of intellectual disability diagnoses by age 10 for each birth cohort and the prevalence ratios in relation to the baseline year 2011, overall and by severity of intellectual disability, and comorbidity of autism and attention-deficit/hyperactivity disorder. The prevalence ratios were stratified and adjusted for associated sociodemographic and perinatal factors.ResultsAmong 1,096,800 individuals, 8,577 were diagnosed with intellectual disability by age 10. Among these, 3,949 (46%) and 2,768 (32%) were also diagnosed with autism and attention-deficit/hyperactivity disorder, respectively, and 4% were diagnosed with profound, 8% severe, 20% moderate, 52% mild, and 16% other/unspecific intellectual disability. The recorded age-10 prevalence of intellectual disability diagnoses increased from 0.64% (95% confidence interval 0.59–0.69%) in 2011 to 1.00% (0.94–1.06%) in 2021, corresponding to an annual prevalence ratio of 1.04 (1.04–1.05). The increase was, however, restricted to mild, moderate, and other/unspecific intellectual disability diagnoses, while the trends for profound and severe intellectual disability diagnoses were stable. The increasing trend was perhaps less pronounced among females and children with diagnosed attention-deficit/hyperactivity disorder, but independent of the co-occurrence of autism. The prevalence ratios did not change with stratification or adjustment for other associated demographic and perinatal factors.ConclusionThe recorded prevalence of diagnosed mild and moderate intellectual disability among 10-year-olds in Sweden has increased over the recent decade. This increase could not be explained by changes in associated sociodemographic or perinatal factors, including birth weight, gestational age, and parental age, migration status, and education at the child’s birth. The increase instead may be due to changes in diagnostic practices in Sweden over time.

Molecular and Clinical Heterogeneity in Hungarian Patients with Treacher Collins Syndrome-Identification of Two Novel Mutations by Next-Generation Sequencing.

Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder with variable penetrance and high genetic and phenotypic heterogeneity. It is caused by pathogenic variants in the TCOF1, POLR1D, POLR1C, and POLR1B genes, and its major characteristic features are malar and mandibular hypoplasia, downward slanting of the palpebral fissures, and conductive hearing loss. In this study, five patients (two males and three females, age range from 2 to 29 years) with TCS were tested by Next-Generation Sequencing (NGS)-based sequencing and clinically characterized. Genetic analyses detected two deletions and one insertion in the TCOF1 gene and one missense variant in the POLR1D gene. Two novel mutations, c.1371_1372insT (p.Lys458*) in the TCOF1 gene and c.295 G>C (p.Gly99Arg) in the POLR1D gene, were identified. Moreover, two already known mutations, c.4369_4373del (p.Lys1457Glufs*12) and c.2103_2106del (p.Ser701Argfs*9) in the TCOF1 gene, were detected. The novel TCOF1 c.1371_1372insT mutation was associated with mild craniofacial manifestations and very rare symptoms of TCS, i.e., developmental delay and moderate intellectual disability. Although incomplete penetrance is a known phenomenon in TCS, surprisingly, the majority of our patients inherited the disease-causing variants from an asymptomatic mother. The unique feature of our study is the observation of causative mutation transmission between asymptomatic family members. Our results expanded the clinical and mutational spectrum of TCS and further confirmed the inter- and intra-familial variability of this disorder.

The effect of the Bilateral Integration exercise program on the cognitive functioning of pupils with moderate intellectual disabilities.

Children with intellectual disability tend to exhibit lower performance in fundamental movement skills, such as locomotor skills, object control skills, and balance, compared to their typically developing peers. Evidence suggests that physical activity programs tailored for individuals with intellectual disabilities can positively influence the development of their motor skills. Similar to typically developing children, physical activity in children with intellectual disabilities stimulates not only physical development, but also brain function, resulting in cognitive benefits. However, the extent of physical activity's impact on the cognitive functioning of this population remains insufficiently explored. The aim of our study was to assess the effectiveness of a motor exercise program based on the Bilateral Integration method implemented for pupils with moderate intellectual disabilities. The sample consisted of 27 pupils with moderate intellectual disability (13 in the intervention group and 14 in the control group) from two special schools in Poland. Pupils in the intervention group participated in a modified version of the Bilateral Integration School Program -a 26-week physical activity program that included both individual and group sessions. The assessment of cognitive functioning, using the Fifth Edition of the Stanford-Binet Intelligence Subtests, was conducted over three time points in both groups: a pre-test before the intervention (T1), a post-test after the intervention phase end (T2) and a follow-up assessment three months after the post-test (T3). Significant effects of the intervention compared to the control group were observed in certain cognitive variables. Repeated measures ANOVA revealed a significant group-by-time interaction for the Nonverbal Visual-Spatial Processing score, Nonverbal Working Memory score, as well as Verbal Fluid Reasoning. The original program based on the Bilateral Integration method proved effective for pupils with moderate intellectual disability. Preliminary results indicate improvements in cognition, particularly in working memory and visual-spatial processing. Further studies are necessary to assess the program's efficacy comprehensively.

Maximizing Potential : 5W+1H Reading Comprehension Strategy for Student with Moderate Intellectual Disability

This study aims to enhance the reading comprehension skills of elementary school students with moderate intellectual disabilities through a single-subject method. In this study, the researchers use the 5W + 1H strategy to help students understand the meaning of the text. The research data was collected using observation guidelines, which then will be analyzed by using pretest-posttest techniques to assess the subject’s reading comprehension skills improvements. Teaching the 5W + 1H principle - which emphasized the question words why and how using visual images and keywords - was found to be effective in enhancing the subject’s reading comprehension. This finding also explained that this method could maximize the potential of students with moderate intellectual disabilities. The instruction on the question words why and how was particularly effective in increasing the subject's understanding of questions as well as leading him to provide correct and contextually appropriate responses. However, using visual images as a learning aid, especially for why and how questions, seemed less effective, as evidenced by the subject's reliance on keywords within the sentence. In the future, this strategy can be employed by educators to enhance reading comprehension skills for students with moderate intellectual disabilities.

Vision Care as A Strategy to Prevent Falls Among People with Moderate or Severe Intellectual Disability in the Hostel Setting in Hong Kong

Background: Factors contributing to the higher fall risk among people with intellectual disabilities (PIDs) are complex due to their discrete patterns of multimorbidity. Visual impairment, such as cataract, was common at old age and could be a crucial risk factor. Given the insufficient evidence regarding this relationship, the present study aimed at investigating this issue in a hostel setting in Hong Kong. Methods: This study was conducted in four hostels which served people with moderate to severe intellectual disability. Health data of residents collected in the year of 2022-23 was utilized for the current analysis. Data included fall risk, assessed by Morse Fall Scale, as well as other health conditions (osteoporosis, osteoarthritis, cataract) and demographics (age and gender) among residents. Results: The sample consisted of 199 residents (85 were males and 114 females), with an age range of 22 to 76 years. Around 40% (85; 42.7%) of them aged above 45 years old. Among the whole sample, cataract was the most common health condition and its prevalence reached 27.14%. Those who aged 45-year or above were 4.61 times (95%CI 2.09-11.07) more likely to have cataract. Bivariate analysis results showed that presence of fall risk was associated with older age (above 45 years old; OR 2.38; 95%CI 1.28-4.49), diagnosis of cataract (OR 3.3; 95%CI 1.71-6.33) and osteoarthritis (OR 12.68; 95%CI 1.70-564.75). Logistic regression analysis further illustrated that cataract (p = 0.04) remained as a significant predictor of fall risk after controlling age, gender, osteoarthritis and osteoporosis in the model. Conclusion: Our data showed that presence of cataract diagnosis was significantly associated with higher fall risk among PIDs in hostel setting. Given cataract was a prevalent condition especially among aging PIDs, early screening and intervention could be crucial components of fall prevention strategy in a hostel setting.

The influence of assistance in home-based exercise programmes for individuals with intellectual disabilities.

Regular physical activity (PA) decreases the risk of comorbidities associated with a sedentary lifestyle in individuals with intellectual disabilities (IDs). They also may experience additional barriers that may prevent PA, including access, proper instruction and support. At-home PA programming is a feasible alternative to long-term adherence. This study aimed to determine (1) how an at-home DVD programme affects PA adherence and (2) the extent to which caregiver support influences PA. Thirty-one adolescent or adult-aged participants with mild or moderate ID were randomised into a DVD or control group exercise intervention. Participants were given autonomy to choose what type of PA modality from the intervention they would like to participate in. Caregiver support during the PA was also measured. The two-way repeated-measures MANOVA demonstrated that the intervention DVD group was statistically significant, with a large effect size in PA minutes (P=0.014, ηP2=0.236) and rate of perceived exertion (P=0.002, ηP2=0.342) compared with the control group. The findings demonstrated that using an adapted DVD increased PA minutes and the rate of perceived exertion without high levels of caregiver support.

The Effect of Edmark Reading Program Functional Words Series Presented with Tablet Computer in Acquiring Functional Reading Skills for Students with Intellectual Disabilities

This study aims to examine the effect of the Edmark Reading Program Functional Words Series, which is presented with a tablet computer, on the acquisition of functional reading skills by three high school students with moderate intellectual disabilities. The design of the study is a multiple-probe model with an inter-subject probe phase, which is one of the single-subject research models. While the dependent variable is identified as functional reading skill, the independent variable of the present study is the Edmark Reading Program Functional Words Series offered via a tablet computer. The participants of the study are three male students with moderate intellectual disability. The starting level of the experimental process of the research, the implementation of the Edmark Reading Program Functional Words Series consisted of monitoring and generalization stages. The data obtained in the research were analyzed and interpreted graphically. As a result of the research, it was found that the Edmark Reading Program Functional Words Series, which was tested with a tablet computer, was effective in acquiring functional reading skills of students with moderate intellectual disability. In addition, the participants of the research were able to generalize the 10 target words that were taught in the real environment as well as in the teaching environment, and they were able to continue reading one and three weeks after the teaching. The interviews conducted to determine the social validity of the research revealed that parents, teachers and participant students expressed positive opinions about the program offered via tablet computer.

Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling

BackgroundSETBP1 Haploinsufficiency Disorder (SETBP1-HD) is characterised by mild to moderate intellectual disability, speech and language impairment, mild motor developmental delay, behavioural issues, hypotonia, mild facial dysmorphisms, and vision impairment. Despite a clear link between SETBP1 mutations and neurodevelopmental disorders the precise role of SETBP1 in neural development remains elusive. We investigate the functional effects of three SETBP1 genetic variants including two pathogenic mutations p.Glu545Ter and SETBP1 p.Tyr1066Ter, resulting in removal of SKI and/or SET domains, and a point mutation p.Thr1387Met in the SET domain.MethodsGenetic variants were introduced into induced pluripotent stem cells (iPSCs) and subsequently differentiated into neurons to model the disease. We measured changes in cellular differentiation, SETBP1 protein localisation, and gene expression changes.ResultsThe data indicated a change in the WNT pathway, RNA polymerase II pathway and identified GATA2 as a central transcription factor in disease perturbation. In addition, the genetic variants altered the expression of gene sets related to neural forebrain development matching characteristics typical of the SETBP1-HD phenotype.LimitationsThe study investigates changes in cellular function in differentiation of iPSC to neural progenitor cells as a human model of SETBP1 HD disorder. Future studies may provide additional information relevant to disease on further neural cell specification, to derive mature neurons, neural forebrain cells, or brain organoids.ConclusionsWe developed a human SETBP1-HD model and identified perturbations to the WNT and POL2RA pathway, genes regulated by GATA2. Strikingly neural cells for both the SETBP1 truncation mutations and the single nucleotide variant displayed a SETBP1-HD-like phenotype.

X-Linked Bilateral Polymicrogyria With Epilepsy andIntellectual Disability Associated With a Novel KIF4A Variant.

We studied three brothers and a maternal half-brother featuring global developmental delay, mild to moderate intellectual disability, epilepsy, microcephaly, and strabismus. All had bilateral perisylvian and perirolandic polymicrogyria, while some also had malformations of the hippocampus (malrotation and dysplasia), cerebellum (heterotopias and asymmetric aplasia), corpus callosum dysgenesis, and brainstem asymmetric dysplasia. Exome sequencing showed that all four patients had a novel variant (c.1597C>T:p.Leu533Phe) on the KIF4A gene on chromosome X. We discuss how this variant is possibly pathogenic and could explain the reported phenotype.

A - 63 Sotos Syndrome: a Case Study

Abstract Objective Sotos syndrome is a genetic disorder characterized by pre and postnatal overgrowth and a non-progressive neurological disorder frequently accompanied by intellectual disability. The estimated prevalence is 1:14,000 live births; however, misdiagnosis is common due to features being attributable to other conditions. This case study highlights the broad range of symptom presentation in individuals with Sotos syndrome and adds to the limited available literature on this rare condition. Method The patient is a 26-year-old female with no prior neuropsychological testing presenting with concerns for cognitive functioning, regression of skills, and emotional/behavioral dysregulation. Concerns were raised for an underlying autism spectrum disorder. She presents with large stature, prominent facial configuration, and hypotonia. Developmental history was significant for delayed motor and language milestones. She has a history of absence seizures in childhood and was evaluated by neurology and medical genetics and diagnosed with Sotos syndrome. Results The patient’s overall intellectual functioning was in the exceptionally low range with a personal strength in verbal skills. Her neurocognitive results and low adaptive skills are indicative of a moderate intellectual disability. The patient’s developmental history, social difficulties, restrictive interests, and repetitive behaviors met criteria for autism spectrum disorder. Another notable finding was frequent starring spells in which she became unresponsive for approximately 15 seconds. Conclusion Delayed motor and language milestones, hypotonia, behavioral problems, and intellectual disability are common in individuals with Sotos syndrome and were present in the patient. Seizures and scoliosis are less common in individuals diagnosed, for which she was referred to a neurologist for further work-up.

Developmental and epileptic encephalopathies after successful treatment of pediatric ALL: A case series and review of literature.

Successful treatment of acute lymphoblastic leukemia (ALL) requires multiagent chemotherapy regimens and central nervous system prophylaxis, including intrathecal methotrexate. Although acute symptomatic seizures can occur during ALL treatment, epilepsy is less common. Furthermore, drug resistant epilepsy (DRE) is rare, presenting with two phenotypes: focal epilepsy, such as temporal lobe, or epileptic encephalopathies (EE), such as Lennox-Gastaut syndrome (LGS). For ALL survivors, the development of DRE has significant impact on morbidity, mortality, and quality of life. We describe four patients with ALL remission, who developed EEs, of which 3 had LGS. Mean age at ALL diagnosis was 1.9 years; range 1.1-2.5 years. All, but one, had normal development prior to ALL. No patient had CNS leukemic involvement. All patients received CNS prophylaxis with intrathecal methotrexate, without cranial radiotherapy. Three had symptomatic methotrexate neurotoxicity during treatment. The mean age at first seizure was 5.6 years; range 3.9-7.5 years, with a mean latency of 3.7 years from ALL diagnosis. All patients developed drug resistant EEs, moderate intellectual disability, and neuropsychiatric co-morbidities. Two patients had a minimal response to corpus callosotomy (CC), and one did not respond the ketogenic diet. Successful treatment of childhood ALL is rarely associated with the development of DRE and EEs. Young age at ALL diagnosis (<3 years) may be a predisposing factor. Palliative treatments, including ketogenic diet and CC have limited benefit in these patients. Individual genetic susceptibility to MTX toxicity is likely related to epileptogenesis, and further research is required for epilepsy biomarkers.

Occupational Therapy Program to Develop Sensorimotor Performance and Adaptive Behavior Skills in Children With Moderate Intellectual Disability

Occupational Therapy Program to Develop Sensorimotor Performance and Adaptive Behavior Skills in Children With Moderate Intellectual Disability

De onbegrepen wereld van matig, ernstig en diep verstandelijk beperkte kinderen met autisme

Children with moderate, severe or profound intellectual disabilities form a small but significant subgroup within the autism spectrum with high and very specific needs. This article reviews their behavioural characteristics and the way they process sensory stimuli and information. Because these children are – unlike people with a normal intelligence – unable to articulate their needs, an attempt is made to give a sketch of their unique experiential world: how do they experience the world, other people and themselves?

Image perception and reception in wordless picture books: Eye movements of children with intellectual disabilities.

Wordless picture books enhance comprehension and vocabulary growth and motivate children with intellectual disabilities (ID) to participate in literary activities. However, the reception of picture books can be challenging because deliberate selective attention processes and recognition of the image's meaning are often delayed. Examining eye movements may help explore these cognitive processes. Therefore, we examined eye movements in 29 children with mild and moderate ID as they explored a wordless picture book, presented on a screen and compared them to 14 typically developing children using a Tobii Pro X3-120 eye tracker. The findings showed that children with moderate ID had shorter fixation duration, fixated less often, and revisited regions of interest less frequently. Our results suggest that children with moderate ID have greater difficulties in selectively directing their attention toward regions of visual input with a high level of informativeness and expend less cognitive effort to understand their meaning.

A Review of Reading Interventions for Students With Moderate and Severe Intellectual Disabilities

A Review of Reading Interventions for Students With Moderate and Severe Intellectual Disabilities